Re: Plcebo Corrected PK/PD

From: "Nick Holford" n.holford@auckland.ac.nz Subject: Re: [NMusers] Plcebo Corrected PK/PD Date: Fri, March 4, 2005 5:56 pm Mats, As I indicated earlier the ability to distinguish the disease progress (aka placebo) from the drug effect will depend on modelling assumptions. Its not clear to me why one must assume zero covariance of alpha and beta so perhaps you could expand more on why this is a necessary condition? It requires a very special design to ensure that Ce does not change with time! So I would always expect changing Ce. If you wish this is some kind of natural cross over design as effect increases and decreases. The problem is usually being able to design the study to define the time course of effect well enough. But my point is that given a suitable model and reasonable parameters which allow separation of the time course of disease progress and drug effect then it is possible to estimate both components independently. Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/